UniProt functional annotation for O14773



	UniProt functional annotation for O14773

UniProt code: O14773.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (PubMed:11054422, PubMed:19038966, PubMed:19038967). Requires substrates with an unsubstituted N-terminus (PubMed:19038966). {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}.

Catalytic activity: Reaction=Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.; EC=3.4.14.9; Evidence={ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967};

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967};

Activity regulation: Inhibited by diisopropyl fluorophosphate (DFP). {ECO:0000269|PubMed:11054422}.

Subunit: Monomer (PubMed:19038967). Interacts with CLN5 (PubMed:19941651). Interacts with CLN3 (PubMed:17237713). {ECO:0000269|PubMed:17237713, ECO:0000269|PubMed:19038967, ECO:0000269|PubMed:19941651}.

Subcellular location: Lysosome {ECO:0000269|PubMed:19941651}. Melanosome {ECO:0000269|PubMed:12643545}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269|PubMed:12643545}.

Tissue specificity: Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.

Ptm: Activated by autocatalytic proteolytical processing upon acidification (PubMed:11054422, PubMed:19038966, PubMed:19038967). N- glycosylation is required for processing and activity (PubMed:19038966, PubMed:19038967). {ECO:0000269|PubMed:11054422, ECO:0000269|PubMed:19038966, ECO:0000269|PubMed:19038967}.

Disease: Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles. {ECO:0000269|PubMed:10330339, ECO:0000269|PubMed:10665500, ECO:0000269|PubMed:11241479, ECO:0000269|PubMed:11339651, ECO:0000269|PubMed:11589012, ECO:0000269|PubMed:12376936, ECO:0000269|PubMed:12414822, ECO:0000269|PubMed:12698559, ECO:0000269|PubMed:14736728, ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:20340139, ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:9295267}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7) [MIM:609270]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR7 patients show difficulty walking and writing, dysarthria, limb ataxia, and cerebellar atrophy. {ECO:0000269|PubMed:23418007}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from bovine.; Evidence={ECO:0000305}; Sequence=AAQ88866.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (PubMed:11054422, PubMed:19038966, PubMed:19038967). Requires substrates with an unsubstituted N-terminus (PubMed:19038966). {ECO:0000269\|PubMed:11054422, ECO:0000269\|PubMed:19038966, ECO:0000269\|PubMed:19038967}.


Catalytic activity:		Reaction=Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.; EC=3.4.14.9; Evidence={ECO:0000269\|PubMed:11054422, ECO:0000269\|PubMed:19038966, ECO:0000269\|PubMed:19038967};
Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269\|PubMed:19038966, ECO:0000269\|PubMed:19038967}; Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269\|PubMed:19038966, ECO:0000269\|PubMed:19038967};
Activity regulation:		Inhibited by diisopropyl fluorophosphate (DFP). {ECO:0000269\|PubMed:11054422}.
Subunit:		Monomer (PubMed:19038967). Interacts with CLN5 (PubMed:19941651). Interacts with CLN3 (PubMed:17237713). {ECO:0000269\|PubMed:17237713, ECO:0000269\|PubMed:19038967, ECO:0000269\|PubMed:19941651}.
Subcellular location:		Lysosome {ECO:0000269\|PubMed:19941651}. Melanosome {ECO:0000269\|PubMed:12643545}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269\|PubMed:12643545}.
Tissue specificity:		Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.
Ptm:		Activated by autocatalytic proteolytical processing upon acidification (PubMed:11054422, PubMed:19038966, PubMed:19038967). N- glycosylation is required for processing and activity (PubMed:19038966, PubMed:19038967). {ECO:0000269\|PubMed:11054422, ECO:0000269\|PubMed:19038966, ECO:0000269\|PubMed:19038967}.
Disease:		Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN2 consists of curvilinear profiles. {ECO:0000269\|PubMed:10330339, ECO:0000269\|PubMed:10665500, ECO:0000269\|PubMed:11241479, ECO:0000269\|PubMed:11339651, ECO:0000269\|PubMed:11589012, ECO:0000269\|PubMed:12376936, ECO:0000269\|PubMed:12414822, ECO:0000269\|PubMed:12698559, ECO:0000269\|PubMed:14736728, ECO:0000269\|PubMed:19201763, ECO:0000269\|PubMed:20340139, ECO:0000269\|PubMed:21990111, ECO:0000269\|PubMed:22612257, ECO:0000269\|PubMed:9295267}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Spinocerebellar ataxia, autosomal recessive, 7 (SCAR7) [MIM:609270]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR7 patients show difficulty walking and writing, dysarthria, limb ataxia, and cerebellar atrophy. {ECO:0000269\|PubMed:23418007}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from bovine.; Evidence={ECO:0000305}; Sequence=AAQ88866.1; Type=Frameshift; Evidence={ECO:0000305};